                1. Field of the Invention        
Embodiments are in the field of quantitative determination of test results from diagnosis methods. They may have application, for example, in biochemical laboratories, such as medical diagnosis, forensic medicine, foodstuff diagnosis, molecular biology, biochemistry, gene technology, and patient monitoring for home users or in pharmacies.                2. Description of Related Art        
Above all in modern medicinal diagnostics, the application of quick tests has greatly gained in significance both for physicians and pharmacists, but also for self-users at home.
For example, in in-vitro diagnostics, so-called lateral flow assays are used in order to produce diagnoses for patients. For this, a body fluid (blood, urine, saliva, sweat) is taken from a patient and applied to a field provided for this purpose on a carrier card or cassette. FIG. 8 shows such a test card or test cassette.
In a card (1) or a cassette (2), as the case may be, there is a test strip (3) made of an absorbent fleece, which is visible through openings (4) and (5). A body fluid (blood, saliva, urine) taken from the test person is applied to these openings. The body fluid spreads on the test strip and flows in the direction of the visible opening (6) thanks to the capillary forces. On the strip, reagents have been applied in stripe-like lines vertical to the direction of flow (antibodies), the proteins from the body fluid reacting with them.
In the view field, there is a colour change reaction on a first line (7)—the capture line, displaying the concentration of the body-own protein in the body fluid to be detected. The sample fluid moves forward to a second line, the control line, and displays the validity of the test.
The tests are based on antibody reactions of specific proteins in the blood.
As a matter of principle, a distinction is made in the lateral flow assays between competitive and non-competitive tests: in non-competitive LFA's, the intensity of the test signal increases with the increased concentration of the analyte. In competitive LFA's, a reduction of the intensity of the test signal comes about in an increase of the concentration of the analyte: with a strong analyte concentration, the control line colours increasingly weakly.
A plethora of such tests with quantitative and qualitative detection exists. In each case, a certain threshold concentration exists, which is detected by means of a colour signal, in which context the statement that a colour change has even taken place is sufficient in qualitative tests (e.g. pregnancy tests) m whereas the analyte concentration correlates with the colour intensity within the test zone (control line) with the analyte concentration. The invention exclusively relates to the detection of quantitative tests. In this context, each test has a specific, yet precisely reproducible interconnection between analyte concentration and colour intensity.
For example, in a heart attack, the protein h-FABP is released into the blood in a concentration of a few nl and can be detected as early as 15 minutes after the infarction. If a drop of blood of a few nanoliters (nl) is placed on the sample field, the following reaction takes place on the test card:
The components of the blood are taken apart (so-called blood plasma), as a result of capillary forces, the h-FABP reaches the antibody line and reacts there with gold-labelled antibodies. They move on to the capture line. In the capture line, a discoloration is triggered, in which context the strength of the discoloration (i.e. the colour intensity) is a measure for the quantity of antibodies. The strength of the infarction results in differing protein concentrations, which in the end causes differing colour intensities of the capture lines: a slight colour intensity means a slight infraction, a strong colour intensity indicates a severe infraction. The coloured antibodies flow on to the control line, which signalises whether the test is valid or not.
So the assessment of the colour intensity gives information about the severity of the incident.
Such tests with quantitative assessment exist in the meantime for various health diagnoses, in the end giving information about the patient's point of care. The biologists' vision is diagnosing or predicting not only heath “incidents” which have already taken place, but also ones forthcoming for the body. In future, it is also to be possible for various diagnoses to be obtained from a small amount of blood or other body fluids on a joint card. The market prospects also appear to be very great because people are increasingly willing to invest in health.
In all these cases, precise quantification of the test result is of great importance.
A number of evaluation devices, so-called readers, are already known for quantitative assessment from the state of the art. For example, EP 1965199 describes an evaluation device for the evaluation of a test sample, in which context electromagnetic radiation of a source of radiation falls onto a test sample inserted into the device, the reflected radiation passes through an opening and is deflected onto the measurement device.
The measurement device described in EP 1965199 and generally customary is a camera system with commercial image recognition and evaluation. Such systems use customary CCD cameras, in which context the images are portrayed in video systems with commercial operating systems. Said systems are available in large quantities. The systems portray the image on a screen, in which context the test strips are portrayed with few pixels (depending on the image evaluation). The colour intensity is evaluated by the colour intensity of the pixels portraying the test strip being analysed in a specific programme. The assessment of the colour intensity depends on a large number of parameters (white balance, lighting etc.). In these methods, the evaluation is however very imprecise. The problem is the precise determination of the concentration of the antibodies, which is mainly caused by the fact that the test strips do not react homogeneously.
A suggestion to solve this problem is disclosed in document US 2005/0095697. In it, the signals are portrayed on CCD lines with direct electronic actuation. In the use of the CCD and direct actuation (slide register), each of the individual photo diodes can be read out directly. As each individual photo diode recognises 256 differing colour intensities, the signal portrayed can be precisely distinguished in 256 grey levels.
The advantage of the direct electronic actuation is that the grey levels are read out directly and, for example, compared with the value which, for example, a white background provides. This solution with a CCD line provides the advantage that the CCD information is processed directly. On the other hand, the electronic efforts are higher than with the commercial systems. One has to acquaint oneself with the direct microprocessor programming. On the other hand, one has the benefit that the entire software necessary can be accommodated in the microprocessor of a mobile appliance and the commercial operating system and permanent software updates can be waived.
But as a line cannot provide an extensive image resolution, a movement of the test field in the transverse direction to the line is necessary for evaluation with the appliance according to US 2005/0095697, this being implemented by detection during the insertion of the card into the shaft. The problematic thing in this context is that the user pushes the card into the shaft at the right speed or the sensor works quickly enough. In this way, this method is also imprecise and the results are not sufficiently reproducible.
An essential difficulty in quantitative diagnoses is thus that, on the one hand, the quantity of antibodies is to be quantified (unlike the test with “digital” statements, e.g. pregnant, yes or no), but, on the other hand, the test strips do not react homogeneously. The causes of this are varied, the concentration in the substance to be applied is not homogeneous, application is not done homogeneously, the position of the control or capture line in the test field is not the same, the line geometry deviates etc.
“AntiAging”
A further problem with the devices is that the measurement reproducibility must be guaranteed over the entire life cycle of the appliance and under various ambient influences (temperature, air humidity). This means that test with the same colour identity must result in the same measurement values under various operating temperatures and also after a number of years. This is technically counteracted by the fact that the lighting elements in the appliance age, with the result that the optical performance decreases in the course of time with constant electricity and in addition the optical performance is a function of the appliance temperature. The receiving components (CCD) manifest a certain dark current and inherent noise, as a result of which the measurement precision is limited. These variables are a function of the temperature and time.
In high-quality laboratory devices, this has been solved by the fact that either the lighting strength of the sources of light is regulated via a monitor function (e.g. a photo diode) and/or the CCD is additionally kept at a constant temperature. For this, it is placed on a Peltier element. A Peltier element cools or heats the carriers, as the case may be. Such elements are comparatively expensive and consume large amounts of electricity, with the result that the use of Peltier elements for tempering in mobile devices is difficult to implement.
“Calibration”
A further difficulty is guaranteeing measurement precision in various appliances for the same test and with differing test batches: there must be a guarantee that the same tests (same type) also provide the same results with differing test batches measured with differing devices. This is guaranteed in high-quality appliances (laboratories) by the fact that a storage medium is enclosed with the tests per batch, containing batch-specific data and being assigned to the test. This problem has yet to be solved for mobile appliances.
“Test Identity”
The number of different tests is permanently increasing. This is why appliances have increasingly been designed for a number of tests. Before starting the measurement, the operator must input the test being measured and also state the results which can be expected. In the appliance, the calibration curves, i.e. the interconnection between measured colour intensity and analyte concentration in the body fluid, have been deposited in the memory for the listed tests. The appliance then accesses experience figures or value tables stored in the appliance. The particularly dangerous thing in this context is that the test identity is mixed up, i.e. a wrong test can be called. This is why it is desirable for the appliance to recognise the kind of test automatically.
“Upgrade Ability”
Up to now, appliances have been designed and calibrated in the factory for certain tests. The appliances cannot be extended for additional tests. Such additional new tests can differ from the existing ones, for example, in various value tables in the allocation between measured colour intensity and analyte concentration in the body fluid and can also manifest differing light absorptions as a result of differing colours in the conversion reaction in the capture line.